Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition

Autor: Jonathan R. LaRochelle, Michelle Fodor, Vidyasiri Vemulapalli, Morvarid Mohseni, Ping Wang, Travis Stams, Matthew J. LaMarche, Rajiv Chopra, Michael G. Acker, Stephen C. Blacklow
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Nature Communications, Vol 9, Iss 1, Pp 1-10 (2018)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-018-06823-9
Popis: Activating mutations of the non-receptor protein tyrosine phosphatase SHP2 can cause cancer. Here the authors present the crystal structure of SHP2E76K, the most frequent cancer-associated SHP2 mutation, which adopts an open-state structure and show that the allosteric inhibitor SHP099 can revert SHP2E76K to its closed, autoinhibited conformation.
Databáze: Directory of Open Access Journals